Radhey M. Singh

Copper-free palladium-catalyzed Sonogashira coupling-annulation: efficient one-pot synthesis of functionalized pyrano[4,3-b]quinolines from 2-chloro-3-formylquinolines.

A convenient, one-pot, copper-free, Pd-catalyzed methodology has been described for the synthesis of 1,3-disubstituted pyrano[4,3-b]quinolines from 2-chloro-3-formylquinolines. Formation of annulated products 3 is attributed to the presence of Pd(OAc)2 and PPh3. Further, PPh3 in the reaction mixture promotes the cyclization by reducing the reaction time and increasing the yield of cyclized product.

Ligand-free palladium-catalyzed facile construction of tetra cyclic dibenzo[b,h][1,6]naphthyridine derivatives: domino sequence of intramolecular C–H bond arylation and oxidation reactions

A ligand-free Pd-catalyzed approach has been developed for the synthesis of dibenzo-fused naphthyridines. The reaction involves a one-pot domino sequence of reactions involving C–H functionalisation and oxidation. The reaction was applicable to a wide range of substrates, giving the required product. Further fluorescence studies were performed where the Stokes shift was found to be dependent on the polarity of the solvent.

Pd catalyzed facile synthesis of cyclopenta[b]quinolin-1-one via sequential Sonogashira coupling and annulation. An unusual mode of ring closure, using sulphur as a soft nucleophile

Pd mediated one pot sequential Sonogashira coupling followed by annulation using o-alkynyl aldehyde is reported. Contrary to the established modes of ring closures, an unusual mode of the initial attack of sulphur across the triple bond occurs leading to a cascade of reactions. The protocol requires just single column chromatography, delivering cyclopenta[b]quinolin-1-one in high yields. Furthermore chemoselective transformations were carried out across annulated precursors.

Morita–Baylis–Hillman reaction of acrylamide with isatin derivatives

Summary The Morita–Baylis–Hillman reaction of acrylamide, as an activated alkene, has seen little development due to its low reactivity. We have developed the reaction using isatin derivatives with acrylamide, DABCO as a promoter and phenol as an additive in acetonitrile. The corresponding aza version with acrylate and acrylonitrile has also been developed resulting in high product yields.

TBAB-catalyzed cascade reactions: facile synthesis of 1-trifluoromethyl-3-alkylidene-1,3-dihydrofuro[3,4-b]quinolines via 5-exo-dig cyclization of o-arylalkynylquinoline aldehydes

A convenient method for the facile synthesis of 1-trifluoromethyl-3-alkylidene-1,3-dihydrofuro[3,4-b]quinolines was developed from the TBAB-catalyzed nucleophilic addition/cyclization reaction of o-arylalkynylquinoline aldehydes with trimethyl trifluoromethyl silane, cesium fluoride, and water; the product was obtained in good to excellent yields. The reaction proceeded smoothly via 5-exo-dig selectivity and anti co-planarity addition, affording Z-selective products in an aerobic atmosphere at room temperature. The dihydrofuroquinoline derivatives formed are structurally related to the well-known furoquinoline alkaloids of the rutaceae family.

Ag(I)-Catalyzed one-pot synthesis of 4-fluorobenzo[b][1,6] naphthyridines and 4-fluoroisoquinolines via iminofluorination of alkynes with Selectfluor

Ag(I)-Catalyzed one-pot synthesis of 4-fluorobenzo[b][1,6]naphthyridines is described from o-alkynylquinolinyl aldehydes through imines in good to excellent yields. Selectfluor is used as a fluorinating reagent and the reaction proceeded at room temperature in an open atmosphere. Reactions employed in this synthesis method are also applied for the synthesis of 8-fluoro-1,6-naphthyridine, 7-fluoro-pyrazolo[4,3-c]pyridine and 4-fluoroisoquinoline derivatives. Standardized conditions were also applied on a gram scale reaction and gave a good yield of the product.

Active methylene compounds (AMCs) controlled facile synthesis of acridine and phenanthridine from morita Baylis–Hillman acetate

We carried out simple and facile syntheses of acridines and phenanthridines from MBH acetates of 2-chloro-quinoline-3-carbaldehydes with active methylene compounds (AMCs). Formation of products was found to be dependent on the functional group of the AMC. For example, ethylcyanoacetate and malononitrile favoured the formation of acridines and cyanoacetamide, and ethyl nitroacetate and malonic esters favoured formation of angularly-fused phenanthridines. The reactions leading to the formation of phenanthridines proceeded through single bond rotation of SN2′ intermediate which was attributed to electronic/steric repulsion between the functional groups of AMCs and the nitrogen of quinoline.

Copper-catalyzed cascade reaction: synthesis of pyrimido[4,5-b]quinolinones from 2-chloroquinoline-3-carbonitriles with (aryl)methanamines

Cu-catalyzed cascade reaction of 2-chloroquinoline-3-carbonitriles with benzyl amines and sodium hydroxide in aerobic atmosphere has been developed for the synthesis of pyrimido[4,5-b]quinoline-4-ones. The reaction proceeds sequentially via Ullmann-coupling and conversion of nitrile to amide followed by nucleophilic addition of amide nitrogen onto iminium carbon and air oxidation. Reagents and substrates are cheap and easily available/accessible. Plausible mechanism of reaction is also discussed.

Alkaloid group of Cinchona officinalis: structural, synthetic, and medicinal aspects

Abstract Of the various natural products isolated so far, cinchona alkaloids hold the supreme position for their various medicinal, synthetic, and catalytic applications. The diverse array of structural features studded with a complete spectrum of biological properties makes them a valuable class of natural products. This chapter summarizes their isolation and structural aspects. Subsequently, important synthesis followed by medicinal properties has been discussed.